Postpartum depression (PPD) occurs in up to 20 percent of postpartum women, and carries consequences that may last a lifetime. Although several psychosocial variables contributing to PPD have been identified, substantial variance in the development of PPD remains when considering these variables alone. The following application focuses on physiological changes occurring during the postpartum period that may influence a woman s recovery from childbirth and her descent into depression. Specifically, the proposed study will investigate the impact of the pro-inflammatory cytokine network on the development of PPD, both directly and via alterations in its bidirectional relationship with the hormones of the hypothalamic-pituitary-adrenal (HPA) axis. The pro- inflammatory response is stimulated in women during labor and delivery and plays a key role in postpartum recovery. Although in non-pregnant and non-postpartum populations, an exaggerated pro-inflammatory response has been linked to the development of depression;its role in influencing the mood of postpartum women has been minimally addressed. Likewise, the HPA axis is in flux during the postpartum period;dysregulation of this system also has been linked to depression in non-pregnant, non-postpartum populations, but, again, its role in the depression of postpartum women is unclear. And finally, no studies to date have investigated whether the bidirectional interaction between inflammatory cytokines and HPA axis hormones may become dysregulated in postpartum women, thereby increasing the risk of PPD. In the following application, healthy women will be visited at home by researchers 6 times for data collection;once during weeks 32-36 of pregnancy, and again on postpartum days 7 and 14, and months 1, 3, and 6. Each time, they will complete surveys on depression and stress, and will provide a blood sample for measurement of pro- and anti- inflammatory cytokines and the hormones of the HPA axis. To gather information on diurnal variability in cytokines and HPA hormones, participants also will collect urine (for cytokines) and saliva (for cortisol) 5 times a day for 2-days preceding the blood draw. Development of depression will be evaluated in light of these variables independently and in relation to each other. It is hypothesized that women who experience an exaggerated pro-inflammatory response will demonstrate dysregulation of the HPA axis and an increased incidence of PPD. Identifying modifiable biological risk factors contributing to PPD will enable health care providers to identify women at risk and ultimately, to develop effective strategies to prevent or reduce the development of this disorder. PUBLIC HEALTH RELEVANCE: Postpartum depression is a potentially devastating disorder that affects a woman during one of the most vulnerable and important times of her life. In this study, we aim to better understand the immunological and hormonal changes that occur in non-depressed postpartum women, and, by comparing these changes to those that occur in women with postpartum depression, identify a biological basis for the disorder.